The implantation of stents has become established as one of the most effective therapeutic measures for the treatment of vascular diseases. Stents have the purpose of performing a stabilizing function in hollow organs of a patient. For this purpose, stents featuring conventional designs have a filigree supporting structure comprising metal braces, which is initially present in a compressed (“crimped”) form for introduction into the body and is expanded at the site of the application. One of the main application areas of such stents is to permanently or temporarily dilate and hold open vascular constrictions, particularly constrictions (stenoses) of the coronary blood vessels. In addition, aneurysm stents are also known, which are used to support damaged vessel walls.
Stents comprise a typically tubular base body having sufficient load-bearing capacity in order to hold the constricted vessel open to the desired extent, with the blood flow continuing without impairment through the lumen thereof. This base body is generally formed by a lattice-like supporting structure, which is composed of struts and allows the stent to be introduced in a compressed state, in which it has a small outside diameter, all the way to the stenosis of the particular vessel to be treated and to be expanded there, for example by way of a balloon catheter, so that the vessel has the desired, enlarged inside diameter.
The stent has a base body made of an implant material. An implant material is a non-living material, which is used for applications in medicine and interacts with biological systems. A basic prerequisite for the use of a material as implant material, which is in contact with the surrounding body area when used as intended, is the body friendliness thereof (biocompatibility). Biocompatibility shall be understood as the ability of a material to evoke an appropriate tissue response in a specific application. This includes an adaptation of the chemical, physical, biological, and morphological surface properties of an implant to the recipient's tissue with the aim of a clinically desirable interaction. The biocompatibility of the implant material is also dependent on the temporal course of the response of the biosystem in which it is implanted. For example, irritations and inflammations occur in a relatively short time, which can lead to tissue changes. As a function of the properties of the implant material, biological systems thus react in different ways. According to the response of the biosystem, the implant materials can be divided into bioactive, bioinert and degradable/resorbable materials.
Implant materials for stents comprise polymers, metallic materials, and ceramic materials (as coatings, for example). Biocompatible metals and metal alloys for permanent implants comprise, for example, stainless steels (such as 316L), cobalt-based alloys (such as CoCrMo cast alloys, CoCrMo forge alloys, CoCrWNi forge alloys and CoCrNiMo forge alloys), technical pure titanium and titanium alloys (such as cp titanium, TiAl6V4 or TiAl6Nb7) and gold alloys. In the field of biocorrodible stents, the use of magnesium or technical pure iron as well as biocorrodible base alloys of the elements magnesium, iron, zinc, molybdenum, and tungsten are proposed.
A biological reaction to polymeric, ceramic or metallic implant materials depends on the concentration, exposure time, and manner in which they are administered. Frequently, the presence of an implant material leads to inflammatory reactions, the trigger of which can be mechanical stimuli, chemical substances, or metabolites.
A key problem of stenting into blood vessels is restenosis as a result of excessive neointimal growth, for example, which is caused by a strong proliferation of the surrounding arterial smooth muscle cells and/or a chronic inflammation reaction. As an alternative or in addition, restenosis can be caused and/or promoted by the physiological effect of releasing the decomposition products of the stent, particularly the biocorrodible stent. For example, the decomposition of magnesium-containing stents creates an alkaline environment, which may result in increased muscular tension of the surrounding vascular muscle. As a result of such increased muscular tension, the cross-section of the stent may decrease or the stent integrity may even be lost prematurely.
Strategies to prevent restenosis focus, for example, on inhibiting the proliferation of surrounding cells through medication, such as by the treatment with active ingredients having an antiproliferative effect (such as cytostatic drugs). The active ingredients can be provided, for example, on the implant surface in the form of a coating. Active ingredients that have to already been proposed or employed in this context are sirolimus or derivatives thereof, or taxanes, such as paclitaxel, or salts thereof.
For use, the stent is typically provided with an active ingredient-releasing coating, wherein it has been found that stents comprising the active ingredient-releasing coating exclusively on the abluminal side of the stent are superior to those stents comprising the active ingredient-carrying coating also on the luminal side.
One problem of such stents having in particular only an abluminal active ingredient-releasing coating (referred to as “drug-eluting stents” or DES) is that part of the active ingredient-releasing coating is uncontrollably lost as a result of the mechanical stress that occurs during crimping and the subsequent dilation at the target site. On the one hand, this causes the quantity of the active ingredient that is in fact available at the target site for use is very difficult to predict, thereby creating the possibility of underdosing. On the other hand, the active ingredients that are employed are active ingredients that have significant potential for side effects, which when applied to an unintended site or released systematically in high volume may have a negative impact on the patient being treated.